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Oxysterols and Bile Acid Act as Signaling Molecules That Regulate Cholesterol Homeostasis: Nuclear Receptors LXR, FXR, and Fibroblast Growth Factor 15/19

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Mammalian Sterols

Abstract

Intricate homeostatic mechanisms in animals enable the metabolic flexibility to maintain stable levels of nutrients despite constant fluctuation in their availability. At the cellular level, metabolites themselves can serve as indicators of metabolic status. Oxysterols and bile acids, first considered merely as the intermediates and the end products of steroidogenesis and cholesterol catabolism, are now well-recognized signaling molecules that regulate the cholesterol and bile acid homeostasis and integrate it with the other physiological processes. They do that primarily by binding to nuclear receptors: liver X receptors (LXRs) and farnesoid X receptor (FXR). Through LXR and FXR, oxysterols and bile acids maintain balanced, finely tuned regulation of the cholesterol and bile acid homeostasis integrated with the fatty acid and glucose metabolism. Furthermore, oxysterol-LXR and BA-FXR-FGF15/19 regulated pathways offer exciting opportunities for treating metabolic diseases and related disorders. In this chapter, I will review our current understanding of the metabolic pathways leading to oxysterols and bile acids and functions of oxysterols and bile acids that are mediated by nuclear receptors LXR and FXR.

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References

  1. Muoio DM, Newgard CB. Obesity-related derangements in metabolic regulation. Annu Rev Biochem. 2006;75:367–401.

    CAS  PubMed  Google Scholar 

  2. Evans RM, Mangelsdorf DJ. Nuclear receptors, RXR, and the big bang. Cell. 2014;157:255–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Simons K, Ikonen E. How cells handle cholesterol. Science. 2000;290:1721.

    CAS  PubMed  Google Scholar 

  4. Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005;438:612.

    CAS  PubMed  Google Scholar 

  5. Sih a CJ, Whitlock JHW. Biochemistry of steroids. Annu Rev Biochem. 1968;37:661–94.

    CAS  PubMed  Google Scholar 

  6. Russell DW. Fifty years of advances in bile acid synthesis and metabolism. J Lipid Res. 2009;50:S120–5.

    PubMed  PubMed Central  Google Scholar 

  7. Miller WL. Steroidogenesis: unanswered questions. Trends Endocrinol Metab. 2017;28:771–93.

    CAS  PubMed  Google Scholar 

  8. Liu J-P, et al. Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Mol Cell Neurosci. 2010;43:33–42.

    CAS  PubMed  Google Scholar 

  9. Goldstein JL, DeBose-Boyd RA, Brown MS. Protein sensors for membrane sterols. Cell. 2006;124:35–46.

    CAS  PubMed  Google Scholar 

  10. Brown MS, Radhakrishnan A, Goldstein JL. Retrospective on cholesterol homeostasis: the central role of Scap. Annu Rev Biochem. 2018;87:783–807.

    CAS  PubMed  Google Scholar 

  11. Espenshade PJ, Hughes AL. Regulation of sterol synthesis in eukaryotes. Annu Rev Genet. 2007;41:401–27.

    CAS  PubMed  Google Scholar 

  12. Brown MS, Goldstein JL. Receptor-mediated endocytosis: insights from the lipoprotein receptor system. Proc Natl Acad Sci. 1979;76:3330.

    CAS  PubMed  Google Scholar 

  13. Calkin AC, Tontonoz P. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat Rev Mol Cell Biol. 2012;13:213.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–40.

    CAS  PubMed  Google Scholar 

  15. Nes WD. Biosynthesis of cholesterol and other sterols. Chem Rev. 2011;111:6423–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Mitsche MA, McDonald JG, Hobbs HH, Cohen JC. Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways. elife. 2015;4:e07999.

    PubMed  PubMed Central  Google Scholar 

  17. Fon Tacer K, Kalanj-Bognar S, Waterman MR, Rozman D. Lanosterol metabolism and sterol regulatory element binding protein (SREBP) expression in male germ cell maturation. J Steroid Biochem Mol Biol. 2003;85:429–38.

    CAS  PubMed  Google Scholar 

  18. Fon Tacer K, Pompon D, Rozman D. Adaptation of cholesterol synthesis to fasting and TNF-alpha: profiling cholesterol intermediates in the liver, brain, and testis. J Steroid Biochem Mol Biol. 2010;121:619–25.

    CAS  PubMed  Google Scholar 

  19. Tacer KF, Haugen TB, Baltsen M, Debeljak N, Rozman D. Tissue-specific transcriptional regulation of the cholesterol biosynthetic pathway leads to accumulation of testis meiosis-activating sterol (T-MAS). J Lipid Res. 2002;43:82–9.

    CAS  PubMed  Google Scholar 

  20. Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse. J Biol Chem. 2002;277:3801–4.

    CAS  PubMed  Google Scholar 

  21. Spady DK, Dietschy JM. Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat. J Lipid Res. 1983;24:303–15.

    CAS  PubMed  Google Scholar 

  22. Rader DJ. Regulation of reverse cholesterol transport and clinical implications. Am J Cardiol. 2003;92:42–9.

    Google Scholar 

  23. Xie C, Lund EG, Turley SD, Russell DW, Dietschy JM. Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration. J Lipid Res. 2003;44:1780–9.

    CAS  PubMed  Google Scholar 

  24. Kandutsch AA, Chen HW, Heiniger HJ. Biological activity of some oxygenated sterols. Science. 1978;201:498.

    CAS  PubMed  Google Scholar 

  25. Brown MS, Goldstein JL. Suppression of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol. J Biol Chem. 1974;249:7306–14.

    CAS  PubMed  Google Scholar 

  26. DeBose-Boyd RA. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res. 2008;18:609–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc Natl Acad Sci. 2007;104:6511.

    CAS  PubMed  Google Scholar 

  28. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXRα. Nature. 1996;383:728–31.

    CAS  PubMed  Google Scholar 

  29. Mutemberezi V, Guillemot-Legris O, Muccioli GG. Oxysterols: from cholesterol metabolites to key mediators. Prog Lipid Res. 2016;64:152–69.

    CAS  PubMed  Google Scholar 

  30. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137–74.

    CAS  PubMed  Google Scholar 

  31. Gonzalez FJ. Nuclear receptor control of enterohepatic circulation. Compr Physiol. 2012;2:2811–28.

    PubMed  PubMed Central  Google Scholar 

  32. Houten S, Auwerx J. The enterohepatic nuclear receptors are major regulators of the enterohepatic circulation of bile salts. Ann Med. 2004;36:482–91.

    CAS  PubMed  Google Scholar 

  33. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. Targeting bile-acid signalling for metabolic diseases. Nat Rev Drug Discov. 2008;7:678.

    CAS  PubMed  Google Scholar 

  34. Makishima M, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284:1362.

    CAS  PubMed  Google Scholar 

  35. Parks DJ, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284:1365.

    CAS  PubMed  Google Scholar 

  36. Wang H, Chen J, Hollister K, Sowers LC, Forman BM. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell. 1999;3:543–53.

    CAS  PubMed  Google Scholar 

  37. Janowski BA, et al. Structural requirements of ligands for the oxysterol liver X receptors LXRα and LXRβ. Proc Natl Acad Sci. 1999;96:266.

    CAS  PubMed  Google Scholar 

  38. Zerbinati C, Iuliano L. Cholesterol and related sterols autoxidation. Free Radic Biol Med. 2017;111:151–5.

    CAS  PubMed  Google Scholar 

  39. Luu-The V. Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol. 2013;137:176–82.

    CAS  PubMed  Google Scholar 

  40. Nelson JA, Steckbeck SR, Spencer TA. Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide. J Biol Chem. 1981;256:1067–8.

    CAS  PubMed  Google Scholar 

  41. Iuliano L. Pathways of cholesterol oxidation via non-enzymatic mechanisms. Chem Phys Lipids. 2011;164:457–68.

    CAS  PubMed  Google Scholar 

  42. Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chem Rev. 2011;111:5944–72.

    CAS  PubMed  Google Scholar 

  43. Crick PJ, et al. The oxysterol and cholestenoic acid profile of mouse cerebrospinal fluid. Steroids. 2015;99:172–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Griffiths WJ, et al. Current trends in oxysterol research. Biochem Soc Trans. 2016;44:652.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Pikukeva I. Cholesterol-metabolizing cytochromes P450: implications for cholesterol lowering AU – Pikuleva, Irina A. Exp Opin Drug Metab Toxicol. 2008;4:1403–14.

    Google Scholar 

  46. Lange Y, Ye J, Strebel F. Movement of 25-hydroxycholesterol from the plasma membrane to the rough endoplasmic reticulum in cultured hepatoma cells. J Lipid Res. 1995;36:1092–7.

    CAS  PubMed  Google Scholar 

  47. Meaney S, Bodin K, Diczfalusy U, Björkhem I. On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation: critical importance of the position of the oxygen function. J Lipid Res. 2002;43:2130–5.

    CAS  PubMed  Google Scholar 

  48. Li-Hawkins J, Lund EG, Turley SD, Russell DW. Disruption of the oxysterol 7α-hydroxylase gene in mice. J Biol Chem. 2000;275:16536–42.

    CAS  PubMed  Google Scholar 

  49. Dzeletovic S, Breuer O, Lund E, Diczfalusy U. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal Biochem. 1995;225:73–80.

    CAS  PubMed  Google Scholar 

  50. Javitt NB. Oxysteroids: a new class of steroids with autocrine and paracrine functions. Trends Endocrinol Metab. 2004;15:393–7.

    CAS  PubMed  Google Scholar 

  51. Björkhem I, et al. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 1998;39:1594–600.

    PubMed  Google Scholar 

  52. Bjorkhem I, Diczfalusy U, Lutjohann D. Removal of cholesterol from extrahepatic sources by oxidative mechanisms. Curr Opin Lipidol. 1999;10:161–5.

    CAS  PubMed  Google Scholar 

  53. Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci. 1999;96:7238.

    CAS  PubMed  Google Scholar 

  54. Björkhem I, et al. From brain to bile: evidence that conjugation and ω-hydroxylation are important for elimination of 24S-hydroxycholesterol (cerebrosterol) in humans. J Biol Chem. 2001;276:37004–10.

    PubMed  Google Scholar 

  55. Kotti TJ, Ramirez DMO, Pfeiffer BE, Huber KM, Russell DW. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci USA. 2006;103:3869.

    CAS  PubMed  Google Scholar 

  56. Vance JE, Hayashi H, Karten B. Cholesterol homeostasis in neurons and glial cells. Semin Cell Dev Biol. 2005;16:193–212.

    CAS  PubMed  Google Scholar 

  57. Adams CM, et al. Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. J Biol Chem. 2004;279:52772–80.

    CAS  PubMed  Google Scholar 

  58. Bodin K, et al. Antiepileptic drugs increase plasma levels of 4β-hydroxycholesterolin humans: evidence for involvement of cytochrome P450 3A4. J Biol Chem. 2001;276:38685–9.

    CAS  PubMed  Google Scholar 

  59. Bodin K, et al. Metabolism of 4β-hydroxycholesterol in humans. J Biol Chem. 2002;277:31534–40.

    CAS  PubMed  Google Scholar 

  60. Pagotto MA, et al. Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney. Mol Cell Endocrinol. 2011;332:253–60.

    CAS  PubMed  Google Scholar 

  61. Li J, Daly E, Campioli E, Wabitsch M, Papadopoulos V. De novo synthesis of steroids and oxysterols in adipocytes. J Biol Chem. 2014;289:747–64.

    CAS  PubMed  Google Scholar 

  62. Heo G-Y, Liao W-L, Turko IV, Pikuleva IA. Features of the retinal environment which affect the activities and product profile of cholesterol-metabolizing cytochromes P450 CYP27A1 and CYP11A1. Arch Biochem Biophys. 2012;518:119–26.

    CAS  PubMed  Google Scholar 

  63. Brown AJ. 24(S),25-Epoxycholesterol: a messenger for cholesterol homeostasis. Int J Biochem Cell Biol. 2009;41:744–7.

    CAS  PubMed  Google Scholar 

  64. Wang Y, et al. 24S,25-Epoxycholesterol in mouse and rat brain. Biochem Biophys Res Commun. 2014;449:229–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Rong S, et al. Expression of SREBP-1c requires SREBP-2-mediated generation of a sterol ligand for LXR in livers of mice. elife. 2017;6:e25015.

    PubMed  PubMed Central  Google Scholar 

  66. Spann NJ, et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell. 2012;151:138–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Heverin M, et al. Studies on the cholesterol-free mouse. Arterioscler Thromb Vasc Biol. 2007;27:2191–7.

    CAS  PubMed  Google Scholar 

  68. Muse ED, et al. Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages. Proc Natl Acad Sci USA. 2018;115:E4680–9.

    CAS  PubMed  Google Scholar 

  69. Sundaram SS, Bove KE, Lovell MA, Sokol RJ. Mechanisms of disease: inborn errors of bile acid synthesis. Nat Clin Pract Gastroenterol Hepatol. 2008;5:456–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Pullinger CR, et al. Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest. 2002;110:109–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Myant NB, Mitropoulos KA. Cholesterol 7 alpha-hydroxylase. J Lipid Res. 1977;18:135–53.

    CAS  PubMed  Google Scholar 

  72. Ishibashi S, Schwarz M, Frykman PK, Herz J, Russell DW. Disruption of cholesterol 7α-hydroxylase gene in mice: I. Postnatal lethality reversed by bile acid and vitamin supplementation. J Biol Chem. 1996;271:18017–23.

    CAS  PubMed  Google Scholar 

  73. Schwarz M, et al. Disruption of cholesterol 7α-hydroxylase gene in mice: II. Bile acid deficiency is overcome by induction of oxysterol 7α-hydroxylase. J Biol Chem. 1996;271:18024–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Arnon R, et al. Cholesterol 7-hydroxylase knockout mouse: a model for monohydroxy bile acid-related neonatal cholestasis. Gastroenterology. 1998;115:1223–8.

    CAS  PubMed  Google Scholar 

  75. Schwarz M, Russell DW, Dietschy JM, Turley SD. Marked reduction in bile acid synthesis in cholesterol 7α-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia. J Lipid Res. 1998;39:1833–43.

    CAS  PubMed  Google Scholar 

  76. Schwarz M, Russell DW, Dietschy JM, Turley SD. Alternate pathways of bile acid synthesis in the cholesterol 7α-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding. J Lipid Res. 2001;42:1594–603.

    CAS  PubMed  Google Scholar 

  77. Duane WC, Javitt NB. 27-hydroxycholesterol: production rates in normal human subjects. J Lipid Res. 1999;40:1194–9.

    CAS  PubMed  Google Scholar 

  78. Li-Hawkins J, Lund EG, Bronson AD, Russell DW. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J Biol Chem. 2000;275:16543–9.

    CAS  PubMed  Google Scholar 

  79. Rose K, et al. Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation. J Biol Chem. 2001;276:23937–44.

    CAS  PubMed  Google Scholar 

  80. Russell DW, Setchell KDR. Bile acid biosynthesis. Biochemistry. 1992;31:4737–49.

    CAS  PubMed  Google Scholar 

  81. Perez M-J, Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol. 2009;15:1677–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Gadaleta RM, Cariello M, Sabbà C, Moschetta A. Tissue-specific actions of FXR in metabolism and cancer. Biochim Biophys Acta. 2015;1851:30–9.

    CAS  PubMed  Google Scholar 

  83. Modica S, Gadaleta RM, Moschetta A. Deciphering the nuclear bile acid receptor FXR paradigm. Nucl Recept Signal. 2010;8:nrs.08005.

    Google Scholar 

  84. Danielsson H, Einarsson K, Johansson G. Effect of biliary drainage on individual reactions in the conversion of cholesterol to taurocholic acid. Eur J Biochem. 1967;2:44–9.

    CAS  PubMed  Google Scholar 

  85. Shefer S, Hauser S, Mosbach EH. 7α-hydroxylation of cholestanol by rat liver microsomes. J Lipid Res. 1968;9:328–33.

    CAS  PubMed  Google Scholar 

  86. Maglich JM, et al. Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes. Genome Biol. 2001;2:research0029.0021.

    Google Scholar 

  87. Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988;240:889.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Giguère V. Orphan nuclear receptors: from gene to function. Endocr Rev. 1999;20:689–725.

    PubMed  Google Scholar 

  89. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science. 2001;294:1866.

    CAS  PubMed  Google Scholar 

  90. O’Malley B. MINIREVIEW: the steroid receptor superfamily: more excitement predicted for the future. Mol Endocrinol. 1990;4:363–9.

    PubMed  Google Scholar 

  91. Kliewer SA, Lehmann JM, Willson TM. Orphan nuclear receptors: shifting endocrinology into reverse. Science. 1999;284:757.

    CAS  PubMed  Google Scholar 

  92. Mangelsdorf DJ, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83:835–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Baker ME. Origin and diversification of steroids: co-evolution of enzymes and nuclear receptors. Mol Cell Endocrinol. 2011;334:14–20.

    CAS  PubMed  Google Scholar 

  94. Blumberg B, Evans RM. Orphan nuclear receptors—new ligands and new possibilities. Genes Dev. 1998;12:3149–55.

    CAS  PubMed  Google Scholar 

  95. Kliewer SA, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998;92:73–82.

    CAS  PubMed  Google Scholar 

  96. McSorley LC, Daly AK. Identification of human cytochrome P450 isoforms that contribute to all-trans-retinoic acid 4-hydroxylation. Biochem Pharmacol. 2000;60:517–26.

    CAS  PubMed  Google Scholar 

  97. Kuro-o M. The klotho proteins in health and disease. Nat Rev Nephrol. 2019;15:27–44.

    CAS  PubMed  Google Scholar 

  98. Apfel R, et al. A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol Cell Biol. 1994;14:7025.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Willy PJ, et al. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 1995;9:1033–45.

    CAS  PubMed  Google Scholar 

  100. Repa JJ, Mangelsdorf DJ. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol. 2000;16:459–81.

    CAS  PubMed  Google Scholar 

  101. Bookout AL, et al. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006;126:789–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995;377:454–7.

    CAS  PubMed  Google Scholar 

  103. Hörlein AJ, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995;377:397–404.

    PubMed  Google Scholar 

  104. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 2000;14:121–41.

    CAS  PubMed  Google Scholar 

  105. Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med. 2003;9:213–9.

    CAS  PubMed  Google Scholar 

  106. Russell DW. Cholesterol biosynthesis and metabolism. Cardiovasc Drugs Ther. 1992;6:103–10.

    CAS  PubMed  Google Scholar 

  107. Forman BM, Ruan B, Chen J, Schroepfer GJ, Evans RM. The orphan nuclear receptor LXRα is positively and negatively regulated by distinct products of mevalonate metabolism. Proc Natl Acad Sci. 1997;94:10588.

    CAS  PubMed  Google Scholar 

  108. Lehmann JM, et al. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 1997;272:3137–40.

    CAS  PubMed  Google Scholar 

  109. Yang C, et al. Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem. 2006;281:27816–26.

    CAS  PubMed  Google Scholar 

  110. Byskov AG, et al. Chemical structure of sterols that activate oocyte meiosis. Nature. 1995;374:559–62.

    CAS  PubMed  Google Scholar 

  111. Muse ED, et al. Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages. Proc Natl Acad Sci. 2018;115:E4680.

    CAS  PubMed  Google Scholar 

  112. Rowe AH, et al. Enhanced synthesis of the oxysterol 24(S),25-epoxycholesterol in macrophages by inhibitors of 2,3-oxidosqualene:lanosterol cyclase. Circ Res. 2003;93:717–25.

    CAS  PubMed  Google Scholar 

  113. Beyea MM, et al. Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol. J Biol Chem. 2007;282:5207–16.

    CAS  PubMed  Google Scholar 

  114. Schultz JR, et al. Role of LXRs in control of lipogenesis. Genes Dev. 2000;14:2831–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Björkhem I. Are side-chain oxidized oxysterols regulators also in vivo? J Lipid Res. 2009;50:S213–8.

    PubMed  PubMed Central  Google Scholar 

  116. Acimovic J, et al. Combined gas chromatographic/mass spectrometric analysis of cholesterol precursors and plant sterols in cultured cells. J Chromatogr B. 2009;877:2081–6.

    CAS  Google Scholar 

  117. Tacer KF, Kuzman D, Seliškar M, Pompon D, Rozman D. TNF-α interferes with lipid homeostasis and activates acute and proatherogenic processes. Physiol Genomics. 2007;31:216–27.

    CAS  Google Scholar 

  118. Lange Y, Steck TL. Quantitation of the pool of cholesterol associated with acyl-CoA:cholesterol acyltransferase in human fibroblasts. J Biol Chem. 1997;272:13103–8.

    CAS  PubMed  Google Scholar 

  119. de Duve C. Tissue fraction-past and present. J Cell Biol. 1971;50:20.

    PubMed  PubMed Central  Google Scholar 

  120. Das A, Brown MS, Anderson DD, Goldstein JL, Radhakrishnan A. Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis. elife. 2014;3:e02882.

    PubMed Central  Google Scholar 

  121. DeBose-Boyd RA, Ou J, Goldstein JL, Brown MS. Expression of sterol regulatory element-binding protein 1c (SREBP-1c) mRNA in rat hepatoma cells requires endogenous LXR ligands. Proc Natl Acad Sci. 2001;98:1477.

    CAS  PubMed  Google Scholar 

  122. Wong J, Quinn CM, Brown AJ. Statins inhibit synthesis of an oxysterol ligand for the liver X receptor in human macrophages with consequences for cholesterol flux. Arterioscler Thromb Vasc Biol. 2004;24:2365–71.

    CAS  PubMed  Google Scholar 

  123. Peet DJ, et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXRα. Cell. 1998;93:693–704.

    CAS  PubMed  Google Scholar 

  124. Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 2007;5:73–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Downes M, et al. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 2003;11:1079–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Li-Hawkins J, et al. Cholic acid mediates negative feedback regulation of bile acid synthesis in mice. J Clin Invest. 2002;110:1191–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Miao B, et al. Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J Lipid Res. 2004;45:1410–7.

    CAS  PubMed  Google Scholar 

  128. Quinet EM, et al. Gene-selective modulation by a synthetic oxysterol ligand of the liver X receptor. J Lipid Res. 2004;45:1929–42.

    CAS  PubMed  Google Scholar 

  129. Wong J, Quinn CM, Brown AJ. Synthesis of the oxysterol, 24(S), 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol. Lipids Health Dis. 2007;6:10.

    PubMed  PubMed Central  Google Scholar 

  130. Hong C, Tontonoz P. Liver X receptors in lipid metabolism: opportunities for drug discovery. Nat Rev Drug Discov. 2014;13:433.

    CAS  PubMed  Google Scholar 

  131. Komati R, et al. Ligands of therapeutic utility for the liver X receptors. Molecules. 2017;22:88.

    PubMed Central  Google Scholar 

  132. Tontonoz P, Mangelsdorf DJ. Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol. 2003;17:985–93.

    CAS  PubMed  Google Scholar 

  133. Kalaany NY, Mangelsdorf DJ. LXRS AND FXR: The Yin and Yang of cholesterol and fat metabolism. Annu Rev Physiol. 2006;68:159–91.

    CAS  PubMed  Google Scholar 

  134. Zhang Y, et al. Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice. J Clin Invest. 2012;122:1688–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Venkateswaran A, et al. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXRα. Proc Natl Acad Sci. 2000;97:12097.

    CAS  PubMed  Google Scholar 

  136. Repa JJ, et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science. 2000;289:1524.

    CAS  PubMed  Google Scholar 

  137. Kennedy MA, et al. Characterization of the human ABCG1 gene: liver X receptor activates an internal promoter that produces a novel transcript encoding an alternative form of the protein. J Biol Chem. 2001;276:39438–47.

    CAS  PubMed  Google Scholar 

  138. Repa JJ, et al. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors α and β. J Biol Chem. 2002;277:18793–800.

    CAS  PubMed  Google Scholar 

  139. Yu L, et al. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem. 2003;278:15565–70.

    CAS  PubMed  Google Scholar 

  140. Mak PA, et al. Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages: a critical role for nuclear liver X receptors α and β. J Biol Chem. 2002;277:31900–8.

    CAS  PubMed  Google Scholar 

  141. Laffitte BA, et al. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci USA. 2001;98:507–12.

    CAS  PubMed  Google Scholar 

  142. Luo Y, Tall AR. Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. J Clin Invest. 2000;105:513–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Zhang Y, Repa JJ, Gauthier K, Mangelsdorf DJ. Regulation of lipoprotein lipase by the oxysterol receptors, LXRα and LXRβ. J Biol Chem. 2001;276:43018–24.

    CAS  PubMed  Google Scholar 

  144. Lo Sasso G, et al. Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. Cell Metab. 2010;12:187–93.

    CAS  PubMed  Google Scholar 

  145. Magida JA, Evans RM. Rational application of macrophage-specific LXR agonists avoids the pitfalls of SREBP-induced lipogenesis. Proc Natl Acad Sci. 2018;115:5051.

    CAS  PubMed  Google Scholar 

  146. Goodwin B, et al. Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-α. Mol Endocrinol. 2003;17:386–94.

    CAS  PubMed  Google Scholar 

  147. Horton JD, Cuthbert JA, Spady DK. Regulation of hepatic 7α-hydroxylase expression and response to dietary cholesterol in the rat and hamster. J Biol Chem. 1995;270:5381–7.

    CAS  PubMed  Google Scholar 

  148. Lofland HB, Clarkson TB, St RW, Clair NDML. Studies on the regulation of plasma cholesterol levels in squirrel monkeys of two genotypes. J Lipid Res. 1972;13:39–47.

    CAS  PubMed  Google Scholar 

  149. Pertsemlidis D, Kirchman EH, Ahrens EH Jr. Regulation of cholesterol metabolism in the dog: I. Effects of complete bile diversion and of cholesterol feeding on absorption, synthesis, accumulation, and excretion rates measured during life. J Clin Invest. 1973;52:2353–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Jelinek DF, Andersson S, Slaughter CA, Russell DW. Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. J Biol Chem. 1990;265:8190–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Pandak WM, et al. Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat. J Biol Chem. 1991;266:3416–21.

    CAS  PubMed  Google Scholar 

  152. Rudel L, Deckelman C, Wilson M, Scobey M, Anderson R. Dietary cholesterol and downregulation of cholesterol 7 alpha-hydroxylase and cholesterol absorption in African green monkeys. J Clin Invest. 1994;93:2463–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Xu G, et al. Unexpected inhibition of cholesterol 7 alpha-hydroxylase by cholesterol in New Zealand white and Watanabe heritable hyperlipidemic rabbits. J Clin Invest. 1995;95:1497–504.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Zelcer N, Hong C, Boyadjian R, Tontonoz P. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009;325:100.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Sallam T, et al. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis. Nature. 2016;534:124.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Zhang L, et al. Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP. elife. 2017;6:e28766.

    PubMed  PubMed Central  Google Scholar 

  157. Hua X, et al. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci. 1993;90:11603.

    CAS  PubMed  Google Scholar 

  158. Hong C, et al. The LXR–Idol axis differentially regulates plasma LDL levels in primates and mice. Cell Metab. 2014;20:910–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Rasheed A, Cummins CL. Beyond the foam cell: the role of LXRs in preventing atherogenesis. Int J Mol Sci. 2018;19:2307.

    PubMed Central  Google Scholar 

  160. Forman BM, et al. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell. 1995;81:687–93.

    CAS  PubMed  Google Scholar 

  161. Laffitte BA, et al. Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J Biol Chem. 2000;275:10638–47.

    CAS  PubMed  Google Scholar 

  162. Goodwin B, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6:517–26.

    CAS  PubMed  Google Scholar 

  163. Lu TT, et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell. 2000;6:507–15.

    CAS  PubMed  Google Scholar 

  164. Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J. 2006;25:1419–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Matsubara T, Li F, Gonzalez FJ. FXR signaling in the enterohepatic system. Mol Cell Endocrinol. 2013;368:17–29.

    CAS  PubMed  Google Scholar 

  166. Kawamata Y, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003;278:9435–40.

    CAS  PubMed  Google Scholar 

  167. Maruyama T, et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002;298:714–9.

    CAS  PubMed  Google Scholar 

  168. Makishima M, et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002;296:1313.

    CAS  PubMed  Google Scholar 

  169. Maglich JM, et al. Nuclear pregnane X receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol. 2002;62:638.

    CAS  PubMed  Google Scholar 

  170. Handschin C, Meyer UA. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys. 2005;433:387–96.

    CAS  PubMed  Google Scholar 

  171. Kok T, et al. Enterohepatic circulation of bile salts in farnesoid X receptor-deficient mice: efficient intestinal bile salt absorption in the absence of ileal bile acid-binding protein. J Biol Chem. 2003;278:41930–7.

    CAS  PubMed  Google Scholar 

  172. Sinal CJ, et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell. 2000;102:731–44.

    CAS  PubMed  Google Scholar 

  173. Yang F, et al. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res. 2007;67:863.

    CAS  PubMed  Google Scholar 

  174. Kim I, et al. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis. 2007;28:940–6.

    CAS  PubMed  Google Scholar 

  175. Kim I, et al. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J Lipid Res. 2007;48:2664–72.

    CAS  PubMed  Google Scholar 

  176. Lee H, et al. FXR regulates organic solute transporters α and β in the adrenal gland, kidney, and intestine. J Lipid Res. 2006;47:201–14.

    CAS  PubMed  Google Scholar 

  177. Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem. 2001;276:28857–65.

    CAS  PubMed  Google Scholar 

  178. Plass JRM, et al. Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump. Hepatology. 2002;35:589–96.

    CAS  PubMed  Google Scholar 

  179. Landrier J-F, Eloranta JJ, Vavricka SR, Kullak-Ublick GA. The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-α and -β genes. Am J Physiol Gastrointest Liver Physiol. 2006;290:G476–85.

    CAS  PubMed  Google Scholar 

  180. Kliewer SA, Mangelsdorf DJ. Bile acids as hormones: The FXR-FGF15/19 pathway. Dig Dis. 2015;33:327–31.

    PubMed  PubMed Central  Google Scholar 

  181. Zhang M, Chiang JYL. Transcriptional regulation of the human sterol 12α-hydroxylase gene (CYP8B1): roles of hepatocyte nuclear factor 4α in mediating bile acid repression. J Biol Chem. 2001;276:41690–9.

    CAS  PubMed  Google Scholar 

  182. Björkhem I, Eriksson M, Einarsson K. Evidence for a lack of regulatory importance of the 12 alpha-hydroxylase in formation of bile acids in man: an in vivo study. J Lipid Res. 1983;24:1451–6.

    PubMed  Google Scholar 

  183. Song CS, et al. Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. J Biol Chem. 2001;276:42549–56.

    CAS  PubMed  Google Scholar 

  184. Pircher PC, et al. Farnesoid X receptor regulates bile acid-amino acid conjugation. J Biol Chem. 2003;278:27703–11.

    CAS  PubMed  Google Scholar 

  185. Gnerre C, Blättler S, Kaufmann MR, Looser R, Meyer UA. Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional binding sites in the CYP3A4 gene. Pharmacogenet Genomics. 2004;14:635–45.

    CAS  Google Scholar 

  186. Strautnieks SS, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet. 1998;20:233–8.

    CAS  PubMed  Google Scholar 

  187. de Vree JM, et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci USA. 1998;95:282–7.

    PubMed  Google Scholar 

  188. Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med. 2004;10:1352–8.

    CAS  PubMed  Google Scholar 

  189. Shaffer EA. Review article: control of gall-bladder motor function. Aliment Pharmacol Ther. 2000;14:2–8.

    CAS  PubMed  Google Scholar 

  190. Chen F, et al. Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter. J Biol Chem. 2003;278:19909–16.

    CAS  PubMed  Google Scholar 

  191. Grober J, et al. Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene: involvement of the farnesoid X receptor/9-cis-retinoic acid receptor heterodimer. J Biol Chem. 1999;274:29749–54.

    CAS  PubMed  Google Scholar 

  192. Love MW, Dawson PA. New insights into bile acid transport. Curr Opin Lipidol. 1998;9:225.

    CAS  PubMed  Google Scholar 

  193. Claudel T, et al. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J Clin Invest. 2002;109:961–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Matsukuma KE, et al. Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase. J Lipid Res. 2006;47:2754–61.

    CAS  PubMed  Google Scholar 

  195. Kast HR, et al. Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids. Mol Endocrinol. 2001;15:1720–8.

    CAS  PubMed  Google Scholar 

  196. Lambert G, et al. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J Biol Chem. 2003;278:2563–70.

    CAS  PubMed  Google Scholar 

  197. Claudel T, et al. Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology. 2003;125:544–55.

    CAS  PubMed  Google Scholar 

  198. Watanabe M, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest. 2004;113:1408–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Pineda Torra I, et al. Bile acids induce the expression of the human peroxisome proliferator-activated receptor α gene via activation of the farnesoid X receptor. Mol Endocrinol. 2003;17:259–72.

    PubMed  Google Scholar 

  200. Inagaki T, et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci USA. 2006;103:3920.

    CAS  PubMed  Google Scholar 

  201. Choi M, et al. Identification of a hormonal basis for gallbladder filling. Nat Med. 2006;12:1253–5.

    CAS  PubMed  Google Scholar 

  202. Holt JA, et al. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 2003;17:1581–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  203. Kurosu H, et al. Tissue-specific expression of βKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007;282:26687–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  204. Fon Tacer K, et al. Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol. 2010;24:2050–64.

    PubMed  PubMed Central  Google Scholar 

  205. Kir S, Zhang Y, Gerard RD, Kliewer SA, Mangelsdorf DJ. Nuclear receptors HNF4α and LRH-1 cooperate in regulating Cyp7a1 in vivo. J Biol Chem. 2012;287:41334–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Yu C, et al. Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J Biol Chem. 2000;275:15482–9.

    CAS  PubMed  Google Scholar 

  207. Ito S, et al. Impaired negative feedback suppression of bile acid synthesis in mice lacking βKlotho. J Clin Invest. 2005;115:2202–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Modica S, et al. Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis. Gastroenterology. 2012;142:355–65.e354.

    CAS  PubMed  Google Scholar 

  209. Degirolamo C, et al. Prevention of spontaneous hepatocarcinogenesis in farnesoid X receptor–null mice by intestinal-specific farnesoid X receptor reactivation. Hepatology. 2015;61:161–70.

    CAS  PubMed  Google Scholar 

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  1. Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Klementina Fon Tacer

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  1. Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Damjana Rozman

  2. Rudolf Schönheimer Institute of Biochemistry, Department of General Biochemistry, University of Leipzig, Faculty of Medicine, Leipzig, Germany

    Rolf Gebhardt

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Fon Tacer, K. (2020). Oxysterols and Bile Acid Act as Signaling Molecules That Regulate Cholesterol Homeostasis: Nuclear Receptors LXR, FXR, and Fibroblast Growth Factor 15/19. In: Rozman, D., Gebhardt, R. (eds) Mammalian Sterols . Springer, Cham. https://doi.org/10.1007/978-3-030-39684-8_6

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